Allogeneic Mesenchymal Stem Cells for Treatment of Experimental Autoimmune Encephalomyelitis

Abstract

The use of allogeneic "universal donor" mesenchymal stromal cells (MSCs) may be a substantial clinical convenience for treatment of autoimmune ailments such as multiple sclerosis. We therefore tested whether allogeneic MSCs can be exploited for treatment of experimental autoimmune encephalomyelitis (EAE) in mice with otherwise intact immune system. Administration of allogeneic Balb/c-derived MSCs to C57Bl/6 mice with pre-established EAE led to a significant decrease in disease score over time comparable to that achieved with syngeneic MSCs, and was correlated with a significant blunting of immune cell infiltration to the spinal cord and reduced circulating levels of interferon-gamma (IFN-gamma) and interleukin-17. Pretreatment of allogeneic MSCs with IFN-gamma increased the expression levels of CCL2 as well as major histocompatibility complex I (MHCI) and MHCII, but also led to complete loss of suppressive activity in vivo that correlated with immune rejection. In conclusion, allogeneic MSCs can suppress the manifestations of EAE, yet retain the potential for alloimmunization.

Comparative study of immune regulatory properties of stem cells derived from different tissues

“…However, the immune modulatory function of BM-MSCs has been documented in graftversus-host disease [4][5][6], autoimmune encephalomyelitis [17], sepsis [3], collagen-induced arthritis, and bowel inflammation [15,16,20]. But whether other SC categories have the ability to exert comparable effects was unknown and our results provide novel information supporting the view that a variety of SCs share the critical aspect of being immune privileged.…”

“…Several SC subtypes, including neural SCs [10] and mesenchymal stromal cells (MSCs) [11][12][13][14], possess regenerative potential and may interact with immune effector cells (IECs), profoundly influencing their function in vitro and in vivo. The immune system plays a critical role in the pathogenesis and progression of a number of degenerative diseases, raising the possibility that SCs may be effective in repairing the damaged organ by promoting cell formation and modulating the associated immune response [6,[14][15][16][17][18][19][20]. Based on this premise, the immunogenicity and immune modulatory properties of SCs have to be carefully characterized to decipher their potential clinical import.…”

“…However, they indirectly activate resident SCs, enhancing the repair of the organ [70][71][72]. Because of these characteristics, therapeutically, MSCs and MSC-like SCs may have to be repeatedly employed to exert their role long-term, in absence of clear evidence of their homing and persistence inside the tissues [14][15][16][17][18][19][20]. Conversely, the delivery of tissue-specific multipotent adult SCs, such as CSCs and LSCs, to the corresponding damaged organ fails to stimulate the resident SCs nested in proximity to or distant from the injured parenchyma [73,74].…”

Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma

“…Bone marrow stromal cells (BMSCs) have recently been shown to suppress harmful immune responses in patients with acute graftversus-host disease (4,5) and in several animal models of allogeneic rejection (6)(7)(8), a variety of autoimmune diseases (9)(10)(11), and lung injury (12)(13)(14)(15). The authors of many of these studies concluded that BMSC-driven immunosuppression results from a shift in Th1/Th2 balance (8,16,17).…”

Immune Regulatory Properties of CD117pos Amniotic Fluid Stem Cells Vary According to Gestational Age

“…There are several reports regarding the beneficial roles of the immunomodulatory effects of different adult SC types, mainly MSCs, in different disease models such as graft-versus-host disease [33], experimental autoimmune encephalomyelitis [34], inflammatory bowel disease [35], and systemic lupus erythematosus [36]. The safety and efficacy of MSC treatments have been validated in clinical trials [37][38][39][40] and many others are currently in progress.…”